Experts eye retina for BSE link

U.S. researchers found infected animals respond more slowly to light and the retina begins to thin

A cow’s eyes are a window to the animal’s brain, say American researchers studying BSE.

In a recently published paper, scientists with Iowa State University and the U.S. Department of Agriculture document how they used retina tests to detect animals infected with the disease months before they showed traditional signs of illness.

Today, their tests are of greater interest to researchers than ranchers, but scientists in Canada and the U.S. say they have potential and could someday assist the beef sector’s efforts to keep BSE off farms, out of slaughterhouses and far away from customers.

“I have the luxury of just worrying about the science,” said Heather Greenlee, a researcher at Iowa State University’s college of veterinary medicine. “I think that at the very least, if there is interest and a will to pursue using the eye for monitoring (BSE) in livestock, I think knowing that the retina changes and when the retina changes would be really useful.”

Researchers have studied the retina, the part of the body that connects the eye to the brain, and its relationship with prion-related diseases for the last decade.

Prions are the misfolded proteins present in cattle with BSE, sheep with scrapie and cervids with chronic wasting disease.

“A lot of them are blind actually,” Stefanie Czub with the Canadian Food Inspection Agency said of BSE-infected cattle. “Because the retina is not actually working anymore.”

Justin Greenlee with the U.S. Department of Agriculture’s National Animal Disease Centre said researchers previously established that abnormal prion proteins are present in the retinas of infected animals.

“I’m excited about it because it works and especially in cattle that don’t seem to accumulate much of the abnormal prion protein outside of the brain and spinal cord, said Justin. “With chronic wasting disease of deer and elk and scrapie in sheep, there’s abnormal prions in the lymph nodes and spleen and tissues like that very early in the disease, so early that I think when we apply our eye stuff to those diseases it’s not as helpful as tests we already have.

“But in the case of cattle, it’s our best guess. It’s the best sample we can look at in a live animal to have useful information.”

International requirements demand Canada test samples from 30,000 cows every year. With no validated test for live animals, BSE surveillance relies brain samples from dead animals. In 2012 and 2014, Canada fell short of its testing goal.

“I think it is a really interesting approach, because it is not invasive,” Czub said of the retina research.

“You don’t need to put the animal down, you don’t need to take brain … you can do this on a live animal. This would be a potential live animal test if they were to work their problems out. That’s what makes it interesting.”

For their tests, U.S. researchers inoculated adult Holstein steers with two different strains of BSE and studied the function and thickness of the retina, taking measurements every three months.

Heather likened the retina tests to a visit to the optometrist, and even borrowed some technology.

“They developed a sort of gun-shaped probe you could just point at the eye (for pediatrics),” she said. “That’s really what allowed us to then implement this in cattle.”

They found infected cattle re-sponded more slowly to a flash of light 12 months after inoculation.

At the same interval, they also observed a thinner retina, Heather said.

These changes were observed up to 11 months before any traditional signs of disease. Their study says it’s the earliest reported clinical signs associated with BSE, demonstrating that the retina is affected by “protein misfolding disorders long thought to be confined to the brain.”

Once infected with BSE, cattle can carry the disease for years before showing signs or falling victim to the disease, as was the case earlier this year when officials confirmed BSE in a deceased Alberta cow born in 2009. That animal was born on the same farm as another at the centre of a 2010 case.

Researchers say the retina has diagnostic potential, although larger studies, using thousands of animals, not dozens, are needed before a test could be brought to the beef industry.

“The problem for North American BSE surveillance is that we are looking not into healthy animals, but we are testing … animals which have neurological problems, animals which have issues in the brain and with that often already in the eyes as well,” said Czub.

“We don’t really know if this test is able to distinguish between a true BSE-infected animal and an animal with another brain infection, like listeria …”

The study notes “technical, logistical and safety limitations” that prevented some data from being collected from cattle in the study.

“If this is the case, if you can’t use every animal in a feedlot setting, then it is not really robust enough to transfer this method …” said Czub.

There are other challenges, but in the meantime — and if nothing else — researchers have a new bar to compare other potential diagnostics to, said Justin.

“Like anything that starts up from fresh, there are stages you go through where first we’d be happy if this worked, then you get it to work and now the problems you deal with are, ‘OK, how do we do more of these in a timely manner and how do we make it so it’s not us that’s doing the work but anybody can do the work?’” he said.

Heather said the information gathered from the BSE project will help other animal research and assist studies probing human prion diseases like Alzheimer’s and Parkinson’s.

For cattle, this information could be employed as another line of defence against BSE at processing facilities, she said.

“I could imagine a situation where either just prior to slaughter or just immediately after slaughter eyes could be used to screen (for BSE), ‘Oh, this eye is within normal and its fine, send that carcass through. … This eye is not within normal. Let’s send it down a different lane and do a little bit more in-depth testing.’ ” she said.

“… For hardcore diagnosis, I think at the end of the day you still need to do the good old-fashioned let’s look for the misfolded prions.”


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